The gut microbiota, obesity and insulin resistance.

The human gut is densely populated by commensal and symbiotic microbes (the "gut microbiota"), with the majority of the constituent microorganisms being bacteria. Accumulating evidence indicates that the gut microbiota plays a significant role in the development of obesity, obesity-associated inflammation and insulin resistance. In this review we discuss molecular and cell biological mechanisms by which the microbiota participate in host functions that impact the development and maintenance of the obese state, including host ingestive behavior, energy harvest, energy expenditure and fat storage. We additionally explore the diverse signaling pathways that regulate gut permeability and bacterial translocation to the host and how these are altered in the obese state to promote the systemic inflammation ("metabolic endotoxemia") that is a hallmark of obesity and its complications. Fundamental to our discussions is the concept of "crosstalk", i.e., the biochemical exchange between host and microbiota that maintains the metabolic health of the superorganism and whose dysregulation is a hallmark of the obese state. Differences in community composition, functional genes and metabolic activities of the gut microbiota appear to distinguish lean vs obese individuals, suggesting that gut 'dysbiosis' contributes to the development of obesity and/or its complications. The current challenge is to determine the relative importance of obesity-associated compositional and functional changes in the microbiota and to identify the relevant taxa and functional gene modules that promote leanness and metabolic health. As diet appears to play a predominant role in shaping the microbiota and promoting obesity-associated dysbiosis, parallel initiatives are required to elucidate dietary patterns and diet components (e.g., prebiotics, probiotics) that promote healthy gut microbiota. How the microbiota promotes human health and disease is a rich area of investigation that is likely to generate fundamental discoveries in energy metabolism, molecular endocrinology and immunobiology and may lead to new strategies for prevention of obesity and its complications.

Shen J ，Obin MS ，Zhao L 《-》

Gut microbiota, intestinal permeability, obesity-induced inflammation, and liver injury.

Frazier TH ，DiBaise JK ，McClain CJ 《-》

Probiotics, prebiotics, energy balance, and obesity: mechanistic insights and therapeutic implications.

Obesity-related disorders derive from a combination of genetic susceptibility and environmental factors. Recent evidence supports the role of gut microbiota in the pathogenesis of obesity, type 2 diabetes mellitus, and insulin resistance by increasing energy harvest from diet and by inducing chronic, low-grade inflammation. Several studies describe characteristic differences between composition and activity of gut microbiota of lean individuals and those with obesity. Despite this evidence, some pathophysiological mechanisms remain to be clarified. This article discusses mechanisms connecting gut microbiota to obesity and fat storage and the potential therapeutic role of probiotics and prebiotics.

Molinaro F ，Paschetta E ，Cassader M ，Gambino R ，Musso G ... -  《-》

Gut microbiota interactions with obesity, insulin resistance and type 2 diabetes: did gut microbiote co-evolve with insulin resistance?

Esteve E ，Ricart W ，Fernández-Real JM 《-》

Gut microbiota controls adipose tissue expansion, gut barrier and glucose metabolism: novel insights into molecular targets and interventions using prebiotics.

Geurts L ，Neyrinck AM ，Delzenne NM ，Knauf C ，Cani PD ... -  《-》